Alcohol & Drugs

Question 1

Cocaine - Mechanism

Answer 1

Mechanism of action is blocking dopamine transporter DAT, increasing levels of dopamine in the synaptic cleft.

Question 2

Amphetamine - Mechanism

Answer 2

1. Binds to DAT, where it is taken up into presynaptic terminal, where it directly stimulates dopamine release.
2. Inhibits MAO to inhibit metabolism of monoamines.

Question 3

Drugs which interfere with ionotropic receptors or ion channels

Answer 3

Alcohol, nicotine, benzodiazepines, ketamine

Question 4

Drugs which interfere with G coupled receptors

Answer 4

Opioids, cannabinoids, y-hydroxybutyrate (GHB)

Question 5

Drugs that target monoamine transporters

Answer 5

Amphetamine, ecstasy, cocaine

Question 6

Opioids - Effects

Answer 6

Euphoria, drowsiness, constipation, pupillary constriction, respiratory depression

Question 7

Opioids - Withdrawal

Answer 7

Piloerection, insomnia, restlessness, dilated pupils, yawning, sweating, abdominal cramps

Question 8

Amphetamine & Cocaine - Effects

Answer 8

Increased energy, insomnia, hyperactivity, euphoria, paranoia, reduced appetite

Question 9

Amphetamine & Cocaine - Withdrawal

Answer 9

Hypersomnia, hyperphagia, depression, irritability, agitation, vivid dreams, increased appetite

Question 10

MDMA - Effects

Answer 10

Increased energy, increased sweating, jaw clenching, euphoria, enhanced sociability, increased response to touch

Question 11

MDMA - Withdrawal

Answer 11

Depression, insomnia, depersonalisation, derealisation

Question 12

Cannabis - Effect

Answer 12

Relaxation, intensified sensory experience, paranoia, anxiety, injected conjunctivae

Question 13

Cannabis - Withdrawal

Answer 13

Insomnia, reduced appetite, irritability

Question 14

Psychedelics - Effects

Answer 14

Perceptual changes, pupillary dilation, tachycardia, sweating, palpitations, tremors, incoordination

No withdrawal syndrome

Question 15

Ketamine - Effects

Answer 15

Euphoria, dissociation, ataxia, hallucinations, muscle rigidity

No withdrawal syndrome

Question 16

AUDIT

Answer 16

Alcohol Use Disorders Identification Test. 10 item questionnaire.
Has been shown to be superior to CAGE and biochemical markers for predicting alcohol problems.
Minimum score = 0, max score = 40.
Score 8 in men or 7 in women indicates a strong likelihood of hazardous or harmful alcohol consumption.
Score of 15 in men or 13 in women is likely to indicate alcohol dependence

Question 17

FAST

Answer 17

Fast Alcohol Screening Test
4 item questionnaire.
Minimum score = 0, max score = 16.
Score for hazardous drinking is 3+.
If the answer to the first question is ‘never’ then the patient is not misusing alcohol,
If the response to the first question is ‘Weekly’ or ‘Daily or almost daily’ then the patient is a hazardous, harmful or dependent drinker. Over 50% of people will be classified using just this one question.

Question 18

FAST Questions

Answer 18

1. MEN: How often do you have EIGHT or more drinks on one occasion?
   WOMEN: How often do you have SIX or more drinks on one occasion?
2. How often during the last year have you been unable to remember what happened the night before because you had been drinking?
3. How often during the last year have you failed to do what was normally expected of you because of drinking?
4. In the last year has a relative or friend, or a doctor or other health worker been concerned about your drinking or suggested you cut down?

Question 19

CAGE

Answer 19

CAGE is a 4 question screening tool. Two or more positive answers suggests problem drinking.

C-Have you ever felt you should Cut down on your drinking?
A-Have people Annoyed you by criticising your drinking?
G-Have you ever felt bad or Guilty about your drinking?
E-Have you ever had a drink in the morning to get rid of a hangover (Eye opener)?

Question 20

SASQ

Answer 20

Single Alcohol Screening Questionnaire.
Asks only one question - when was the last time you had more than x alcoholic drinks in one day? (Where x is 8 for men and 6 for women).
An answer of within 3 months indicates harmful or hazardous drinking.

Question 21

Acamprosate

Answer 21

NMDA glutamate receptor antagonist and a positive allosteric modulator of GABA-A receptors.
Effective at decreasing alcohol withdrawal cravings.
No potential for abuse or dependence.
Overdose is not fatal, but chronic overdose can result in hypercalcemia.
ADR: diarrhoea most common (dose-related and usually transient).

Question 22

Naltrexone

Answer 22

Reversible competitive antagonist at µ and ĸ receptors (δ receptor antagonist to a lesser extent).
Half-life = 4-6 hours.
Reduces both the rewarding effects of alcohol and craving for it.
Low incidence of common adverse events, virtually no abuse potential and patients do not develop tolerance.
ADRs: Nervousness, anxiety, insomnia, headache, sleep disorders, restlessness, arthralgia, myalgia, abdominal pain, abdominal cramps.
Can be started in patients still drinking.

Question 23

Disulfiram

Answer 23

Blocks the conversion of acetaldehyde to acetate by binding irreversibly to aldehyde dehydrogenase. This leads to an unpleasant build-up of acetaldehyde in the blood and results in symptoms such as abdominal colic, flushing, anxiety, dizziness, tachycardia, vomiting and headache. Symptoms start 5-15 minutes after drinking alcohol and last for several hours producing symptoms of nausea and headache.
If large doses of alcohol are consumed whilst receiving disulfiram treatment, collapse, cardiac arrhythmias and even death can occur.
Treatment should be started at least 24 hours after the last drink. Patients must not consume alcohol whilst taking disulfiram.
Contraindications include - psychosis, suicidal risk, severe personality disorder, consumption of alcohol, previous history of CVA, and uncompensated cardiac failure.

Question 24

Alcohol - Withdrawal duration

Answer 24

The initial signs and symptoms of withdrawal begin from 3-12 hrs after drinking stops.
Symptoms peak between 24-48 hours and can last up to 14 days.
Withdrawal seizures (usually generalised) typically occur 12-18 hours after the last drink.
Note that withdrawal symptoms and seizures may occur before blood alcohol levels reach zero.

Question 25

Delirium Tremens - Symptoms

Answer 25

Occurs in 3-5%. Usually occurs 3-4 days following alcohol cessation. Mortality rate is 10-20% if untreated.

Main symptoms:
Clouding of consciousness / confusion
Vivid hallucinations, particularly visual and tactile
Marked tremor

Other symptoms = Autonomic hyperactivity, tachycardia, HTN, sweating, fever, paranoid delusions, agitation, insomnia

Question 26

Delirium Tremens - Risk Factors

Answer 26

• abnormal liver function
• old age
• severity of withdrawal symptoms
• concurrent medical illness
• heavy alcohol use / severe dependence
• self-detox (no medical input)
• previous history of DT
• low potassium
• low magnesium
• thiamine deficiency

Question 27

Treatment of Alcohol Withdrawal

Answer 27

Alcohol enhances the effect of GABA on GABA-A, decreasing overall brain excitability. Chronic exposure results in a compensatory decrease of GABA-A neuroreceptor response to GABA. As a result when people stop drinking their brains become very excitable. For this reason benzodiazepines are the main stay of treatment. Diazepam first-line (lorazepam, oxazepam or temazepam in liver disease).

Thiamine to prevent Wernicke’s encephalopathy. Should be parenteral if they are in a hospital setting or if Wernicke’s is suspected. Give for 5 days and then oral treatment for as long as necessary (where diet inadequate or drinking is resumed).

If an antipsychotic is required, haloperidol is the treatment of choice.

Long-acting benzodiazepines are effective in preventing withdrawal seizures and should be used as prophylaxis in those with a history of this.

Question 28

Wernicke’s - Symptoms

Answer 28

Characterised by the triad of global confusion, ophthalmoplegia, and ataxia.
Other symptoms = hypothermia, hypotension, memory disturbance, coma.

Question 29

Wernicke’s - Cause

Answer 29

Results from prolonged thiamine deficiency, which can occur in:
- Alcohol dependence
- Anorexia nervosa
- Following gastric surgery
- Malignancy
- AIDS
- Hyperemesis gravidarum
- Prolonged total parenteral nutrition

Question 30

Wernicke’s - Pathology

Answer 30

The lesions occur in a symmetrical distribution in structures surrounding the third ventricle, aqueduct, and fourth ventricle. The mammillary bodies are involved in up to 80% of cases, and atrophy of these structures is specific for Wernicke’s encephalopathy.
Pathological features include neuronal loss and demyelination in periventricular grey matter, and haemorrhage and small vessel proliferation in the mamillary bodies, thalamus, cerebellar vermis, and pons.

Question 31

Wernicke’s - Treatment

Answer 31

IV thiamine (vitamin B1), as oral forms of B1 are poorly absorbed. Of those untreated, 80% go on to develop Korsakoff’s syndrome .

IV glucose should be avoided when thiamine deficiency is suspected as it can precipitate or exacerbate Wernicke’s.

With treatment, ophthalmoplegia and confusion usually resolve within days but the ataxia, neuropathy, and nystagmus may be prolonged or permanent.

Question 32

Korsakoff’s - Features

Answer 32

Chronic syndrome characterised by impaired recent memory and anterograde memory in an alert and responsive patient. It is caused by prolonged thiamine (vitamin B1) deficiency and follows Wernicke’s encephalopathy. Other features include lack of insight, apathy, and confabulation.

Intelligence on the WAIS is preserved. Episodic memory is characteristically severely affected. Semantic memory is variably affected. Implicit aspects of memory, including the response to priming and perceptuomotor (procedural) memory are preserved. Immediate memory tested with the digit span is normal, but information can be retained for at most a few minutes.

Question 33

Korsakoff’s - Cause

Answer 33

Thiamine is used in the brain to metabolise glucose. When deficient, a build-up of glucose occurs, which is toxic and causes neuronal loss. The main areas affected in Korsakoff’s syndrome are the mamillary bodies.

Question 34

Opioid - Withdrawal Timing

Answer 34

Withdrawal symptoms may develop upon abrupt discontinuation of opioids, after as little as 5 days of regular and uninterrupted opioid use.

For short-acting opioids (eg, heroin), acute withdrawal symptoms usually begin 4-6 hours after the last dose, peak in 32-72 hours, and diminish over the next 3 to 5 days.

For longer-acting opioids (eg, methadone) acute symptoms occur within 30 to 72 hours after last dose (although anxiety may occur before this), peak at day 4-6, and resolve over the next 10 days or so.

Question 35

Opioid - Pharmacology

Answer 35

The opioid receptors (µ, k, and δ) are G protein-coupled receptors.

The key opioid receptor subtype is µ, which mediates euphoria, as well as respiratory depression, and is the main target for opioids.
The k receptor is involved in mood regulation.
The delta (δ) receptor is involved in anxiolysis.
All three are involved in analgesia.

Question 36

Opioid Addiction - Pathophysiology

Answer 36

Dopaminergic cells within the VTA (ventral tegmental area) produce dopamine, which is released into the nucleus accumbens upon stimulation of μ receptors, producing the euphoria and reward that helps drive repeated use. With repeat opioid exposure, μ receptors in the ventral tegmental area neurons become less responsive to opioid binding and less dopamine is released. This causes dysphoria and depressed mood and contributes to drug craving.

Question 37

Methadone

Answer 37

Full agonist targeting µ receptors (some action against k and δ)
Half-life = 15-22 hr.
Can cause respiratory depression.
Can effect QTc.
Used in pregnancy.

Question 38

Buprenorphine

Answer 38

Partial agonist targeting µ receptors (also a partial k agonist or functional antagonist (possibly with antidepressant effects), and a weak δ antagonist.
Half-life = 24-42 hr (PO).
Very high affinity for µ receptor (5 times that of morphine).
Metabolised by CYP3A4/5.
Safer than methadone in terms of resp depression, less euphoria.
Can precipitate withdrawal.

Question 39

Naloxone

Answer 39

Antagonist targeting all opioid receptors
Half-life = 30-120 minutes.
Active within minutes.
Associated with noncardiogenic pulmonary oedema in up to 3.5% of cases.

Question 40

Clonidine & Lofexidine

Answer 40

Alpha-2 adrenergic agonists.
Used to help opioid withdrawal symptoms (those associated with the NA system, including sweating, shivering, and runny nose and eyes).
Lofexidine has less of an hypotensive effect than clonidine.

Question 41

Noradrenergic Symptoms in Opioid Withdrawal

Answer 41

Locus coeruleus (in pons) has a high density of noradrenergic neurons that possess μ-opioid receptors. It is involved in the stimulation of wakefulness, blood pressure, and breathing, and in overall general alertness.

Exposure to opioids results in heightened neuronal activity in these cells. If opioids are not present to suppress the increased activity, increased amounts of NA are released and withdrawal symptoms appear (eg, jitters, anxiety, muscle cramps, diarrhoea).

Question 42

PCP

Answer 42

Phencyclidine (angel dust). Hallucinogenic.
Leads to illusion of euphoria, omnipotence, superhuman strength, and social and sexual prowess.
NMDA receptor antagonist (like ketamine) with dissociative properties.
Formerly used for anaesthesia and analgesia without triggering cardiorespiratory depression.
Intoxication = violent behavior, nystagmus, tachycardia, hypertension, anesthesia, analgesia.
Intoxication is best managed with benzodiazepines along with supportive measures for breathing and circulation.